Detecting and quantifying cryptic HIV replication

Abstract

The present invention relates to a novel method for detecting efficient cryptic HIV replication in a patient who receives a suppressive antiviral therapy followed by administration of the HIV integrase inhibitor in an effective amount for intensifying the suppressive antiviral therapy, and has undetectable plasma viremia prior to the administration of the HIV integrase inhibitor. The method comprises making a pre-intensification measurement and one or more post-intensification measurements of the concentration of an episomal artifact in samples from the patient, and computing a pre-intensification HIV infection success ratio (R). A pre-intensification HIV infection success ratio (R) sufficiently close to 1 indicates that the patient has the efficient cryptic HIV replication. The method may further comprise quantifying the efficient cryptic HIV replication.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 607,772, filed Mar. 7, 2012, the content of which is incorporated herein by reference in its entirety for all purposes.REFERENCE TO U.S. GOVERNMENT SUPPORT[0002]This work is supported by grants from the National Institute of Allergy and Infectious Diseases (Award Numbers R21AI078842, RO1 AI087135 and P30 AI078498). The United States has certain rights in the invention.FIELD OF THE INVENTION[0003]The invention relates generally to detection and quantification of cryptic human immunodeficiency virus (HIV) replication in patients receiving a suppressive antiviral therapy.BACKGROUND OF THE INVENTION[0004]While numerous antiviral drugs have been developed and approved for treating HIV patients, none of them eliminates HIV completely from the patients. Rather, these antiviral drugs suppress HIV replication in the patients, and are often used in combination to achieve best...

AI Technical Summary

Benefits of technology

[0014]In one embodiment, the method may further comprise computing, on at least one processor, the pre-intensification HIV infection success ratio (R) based on one or more values selected from the group consisting of a death rate of actively infected cells (a), a rate of production of actively infected cells by processes other than infection (ye), ratio-reduction in R following the intensification (ηII), a ratio of the probability of the episomal artifact formation during an infection event when the HIV integrase inhibitor is not present to the probability of the episomal artifact formation when the HIV integrase inhibitor interrupts an infection event (φ), probability of the episomal artifact formation when the HIV integrase inhibitor interrupts an infection event (kII), a decay rate of the episomal artifact (δ), a post-intensification peak concentration of the episomal artifact (Cp), a concentration of peripheral blood mononuclear cells (PBMCs) in a whole blood sample (PMBCm), an effective volume of the patient (Ve), one or more measurements of plasma viral load v(t), and the associated measurement times (t).

[0015]In another embodiment, the method may further comprise computing, on at least one processor, the pre-intensification HIV infection success ratio (R) based on one or more values selected from the group consisting of a death rate of actively infected cells (a), a rate of production of actively infected cells by processes other than infection (ye), ratio-reduction in R following the intensification (ηII), a ratio of the probability of the episomal artifact formation during an infection event when the HIV integrase inhibitor is not present to the probability of the episomal artifact formation when the HIV integrase inhibitor interrupts an infection event (φ), probability of the episomal artifact formation when the HIV integrase inhibitor interrupts an infection event (kII), and a decay rate of the episomal artifact (δ).

[0016]According to anther aspect of the present invention, a system is provided for each method of the present invention. A system for detecting efficient cryptic HIV replication in a patient comprises at least one processor and a compute readable medium coupled to the at least one processor, having instructions which when executed cause the at least one processor to compute a pre-intensification HIV infection success ratio (R). The patient receives a suppressive antiviral therapy not containing an HIV integrase inhibitor followed by administration of the HIV integrase inhibitor in an effective amount for intensifying the suppressive antiviral therapy, and has undetectable plasma viremia prior to the administration of the HIV integrase inhibitor. The pre-intensification HIV infectio

Problems solved by technology

While numerous antiviral drugs have been developed and approved for treating HIV patients, none of them eliminates HIV completely from the patients.

The activation of reservoir cells, which does not involve a new round of reverse transcription, does not result in the production of new viral mutants, and cannot by itself drive the evolution of antiviral resistance.

However, the use of 2-LTR as a

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